A person takes more than 600 million breaths over the course of their life. Every breath stretches the lungs tissues with each inhale and relaxes them with each exhale.

Now, a new research from the Wyss Institute at Harvard University has revealed that this constant pattern of stretching and relaxing generates immune responses against invading the virus.

Their study reveals that the act of breathing generates immune responses that kill invading pathogens. During an experiment, a human lung chip that mimics the mechanical forces of breathing killed flu bugs. The discovery could lead to developing better medications for respiratory diseases, including COVID.

They also identified several drugs that reduced the production of inflammatory cytokines in infected Alveolus Chips, which could be useful in treating excessive inflammation in the lung. Based on these studies, one of those drugs was licensed to Cantex Pharmaceuticals for the treatment of COVID-19 and other inflammatory lung diseases.

As the early phases of the COVID-19 pandemic made painfully clear, the lung is a vulnerable organ where inflammation, in response to infection, can generate a cytokine storm that has deadly consequences. However, the lungs are also very complex, and it is difficult to replicate their unique features in the lab.

“This research demonstrates the importance of breathing motions for human lung function, including immune responses to infection, and shows that our Human Alveolus Chip can be used to model these responses in the deep portions of the lung, where infections are often more severe and lead to hospitalization and death,” says co-first author Dr. Haiqing Bai from Harvard’s Wyss Institute in a university release.

“The model can also be used for preclinical drug testing to ensure that candidate drugs actually reduce infection and inflammation in functional human lung tissue,” Dr. Bai adds.

The lung chip will provide new information on how lung tissues react to respiratory viruses that have pandemic potential and test potential treatments.

Researchers filled the channel lined by alveolar cells with air, while supplying the blood vessel channel with a flowing culture medium containing nutrients that are normally delivered by the blood. Scientists separated the channels using a porous membrane that allowed molecules to flow between them.

The researchers then infected these breathing Alveolus Chips with H3N2 influenza by introducing the virus into the air channel. They observed the development of several known hallmarks of infection, including the breakdown of junctions between cells.

Infection also led to much higher levels of multiple inflammatory cytokines in the blood vessel channel. In addition, the blood vessel cells of infected chips expressed higher levels of immune cells. The results confirmed that the Alveolus Chip could mount an immune response against H3N2 that replicate what happens in the lung of human patients infected with flu virus.

The team then carried out the same experiment without mechanical breathing motions. To their surprise, chips exposed to breathing motions ​​had 50% less viral mRNA in their alveolar channels and a significant reduction in inflammatory cytokine levels compared to static chips. Genetic analysis revealed that the mechanical strain had activated molecular pathways related to immune defense and multiple antiviral genes, and these activations were reversed when the cyclical stretching was stopped.

(Inputs from agencies)


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